HFIP as a versatile solvent in resorcin[ n]arene synthesis

Abstract

Herein, we present 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as an efficient solvent for synthesizing resorcin[n]arenes in the presence of catalytic amounts of HCl at ambient temperature and within minutes. Remarkably, resorcinols with electron-withdrawing groups and halogens, which are reported in the literature as the most challenging precursors in this cyclization, are tolerated. This method leads to a variety of 2-substituted resorcin[n]arenes in a single synthetic step with isolated yields up to 98%.

Keywords: HFIP; cavitand; cyclization; hydroxyalkylation; resorcinarenes.

Scheme 1

Resorcin[n]arene synthesis.

Scheme 2

Scope of resorcin[n]arene synthesis using HFIP. ^aAll reactions were performed with resorcinol (1.0 mmol), aldehyde (1.0 mmol), and HCl (30 mol %) in HFIP (5 mL) at room temperature, and the yields of the reactions are given as isolated yields. ^bGram-scale reaction (1.10 g of resorcinol). ^cReaction time increased to 24 h. ^dAll reactions were performed at 50 °C.

Figure 1

(a) Control experiment testing deiodination of 2-iodoresorcinol. (b) Molecular crystal structure of chlorinated resorcin[4]arenes 1h and 1i, and carboxylic acid-containing 1s at 100 K. Thermal ellipsoids are set at 50% probability level.